rs10490911

Positions:

• chr10-116776588-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330164.2(HSPA12A):​c.91+58347A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 152,290 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.019 (60 hom., cov: 33)
• Consequence: HSPA12A NM_001330164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

Genes affected

HSPA12A (HGNC:19022): (heat shock protein family A (Hsp70) member 12A) Predicted to enable ATP binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSPA12A	NM_001330164.2	c.91+58347A>G		intron_variant
HSPA12A	XM_005269673.6	c.88+58347A>G		intron_variant
HSPA12A	XM_011539579.3	c.88+58347A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSPA12A	ENST00000635765.1	c.91+58347A>G		intron_variant		5
HSPA12A	ENST00000674167.1	c.-124+58347A>G		intron_variant
HSPA12A	ENST00000674197.1	c.88+58347A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2873 AN: 152172 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00989

Gnomad OTH AF: 0.0163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0190 AC: 2887 AN: 152290 Hom.: 60 Cov.: 33 AF XY: 0.0205 AC XY: 1527 AN XY: 74452

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.00933

Gnomad4 FIN AF: 0.0378

Gnomad4 NFE AF: 0.00989

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0133 Hom.: 1

Bravo AF: 0.0182

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10490911; hg19: chr10-118536099;